Release of lysosomal hydrolases during simulated extracorporeal circulation.
Contact with surfaces results in activation of formed blood elements. This study demonstrates that during extracorporeal circulation, release of lysosomal enzymes occurs concomitantly with platelet granule secretion. Fresh, heparinized human blood was recirculated for 2 hours at 1,000 ml/min at 37 degrees C in silicone rubber circuits containing a membrane oxygenator (0.85 m2). The plasma levels of a platelet-specific protein, low affinity platelet factor 4 (LA-PF4), rose from less than 0.5 to 16 +/- 3 SEM microgram/ml plasma, indicating extensive release of platelet alpha granule contents. Concurrently, plasma activity of acid phosphatase and N-acetyl-beta-glucosaminidase increased nearly fivefold. Platelet inhibition prevented release of LA-PF4 and reduced acid phosphatase levels, but failed to alter the levels of N-acetyl-beta-glucosaminidase. Lidocaine (10 to 20 microgram/ml), however, prevented the rise in N-acetyl-beta-glucosaminidase activity and diminished acid phosphatase levels without altering secretion of LA-PF4. The failure of platelet inhibitors to block the increase in N-acetyl-beta-glucosaminidase, and the efficacy of lidocaine to do so without altering LA-PF4 secretion, suggest that leukocytes, not platelets, are the primary source of this lysosomal enzyme. Although acid phosphatase activity measured in plasma my be derived from leukocytes, platelet membranes, and not lysosomes, appear to be a more likely source. Release of hydrolytic enzymes from formed blood elements during cardiopulmonary bypass may cause endothelial cell injury and thus contribute to the increased vascular permeability associated with extracorporeal circulation.
D000118:Acetylglucosaminidase / Q000097:blood; D000135:Acid Phosphatase / Q000097:blood; D005112:Extracorporeal Circulation; D006867:Hydrolases / Q000378:metabolism*; D007781:Lactoferrin / Q000097:blood; D008247:Lysosomes / Q000201:enzymology*; D010107:Oxygenators, Membrane; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000032:analysis; D001616:beta-Galactosidase / Q000097:blood
D010978:Platelet Factor 4; D006867:Hydrolases; D000135:Acid Phosphatase; D001616:beta-Galactosidase; D000118:Acetylglucosaminidase; D007781:Lactoferrin